Our long-term objective is to use mechanistic information about synaptic interactions between individual identified neurons and groups of neurons to describe the properties of the network in which they are embedded. For this purpose, we use the goldfish Mauthner (M-) cell, which triggers a defined motor behavior, the startle response, and the medullary networks which control its excitability and responsiveness to sensory inputs. Two aims are concerned with the feedforward inhibitory network which sets M-cell threshold. They are: 1) to compare the strengths of the synaptic connections between a single inhibitory interneuron and both H-cells, and 2) to analyze quantitatively paired pulse depression, to determine if the probability of transmitter release at individual active zones varies independently as a function of prior activity. Simultaneous pre- and postsynaptic intracellular recordings, quantal analysis, and dye injections to reconstruct the synaptic connections will be used. A third aim is to analyze inhibitory synaptic noise in the M-cell, to determine its effect, which reflects the state of the presynaptic network, on synaptic transfer functions. Synaptic noise will be recorded in current or voltage clamp and analyzed statistically. Two other aims are related to long-term modulation of neural networks. One is to analyze the long-term depression and potentiation of eighth nerve evoked excitatory postsynaptic potentials (EPSPs) observed in the M-cell after tetanizing of these inputs. Conditioning and test stimulus strengths will be varied independently, and the conditioning stimulus will be paired in some cases with another source of dendritic depolarization. We will also ask if NMDA receptor activation contributes to the potentiation. The last aim is to analyze the effects of endogenous peptides, namely cholecystokinin and FMRFamide, on M-cell membrane properties and on synaptic transmission, using electrophysiological techniques similar to those for the other aims. These experiments are concerned with mechanisms regulating synaptic transmission and its plasticity, which are critical to numerous health-related issues, such as learning and memory and developmental and environmental modifications of nervous system function. They should also provide general information relevant to principles of neural network organization in other vertebrates, including humans.